An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature.

BACKGROUND: Glucocorticoid resistance is a rare, sporadic or familial condition caused by mutation of the gene encoding the glucocorticoid receptor (GR). Clinically it is characterized by symptoms developed due to local, tissue-specific, or generalized partial insensitivity to glucocorticoids. CASE PRESENTATION: A 31-year-old woman was evaluated because of infertility at the Endocrine Unit of the 2nd Department of Medicine, Semmelweis University. During her laboratory investigations, elevated serum and salivary cortisol were observed which failed to be suppressed after administration of 1 mg dexamethasone. 24 h urinary cortisol was increased, but a normal midnight serum cortisol was detected suggesting a maintained circadian rhythm. Plasma dehydroepiandrosterone-sulfate and androstendione levels were also elevated. Repeated plasma ACTH measurements indicated slightly elevated or normal values. Bone mineral density was normal. All laboratory results confirmed the diagnosis of glucocorticoid resistance. Genetic counseling followed by Sanger sequencing of the coding region of the gene encoding human glucocorticoid receptor was performed and a missense mutation (Arg714Gln, R714Q) in a heterozygous form was detected. Following family screening, the same mutation was found in her clinically-healthy 35-year-old sister who had no fertility problems.This variant was not detected in more than 60 patients and controls tested either for glucocorticoid resistance or Cushing's syndrome in our Laboratory and it was absent in Exome Variant Server, HumanGene Mutation Database and ExAC databases. CONCLUSIONS: Our case fulfils the diagnostic criteria of glucocorticoid resistance, also named Chrousos syndrome. The glucocorticoid receptor gene mutation detected in our patient has been already reported in a 2-year-old child with hypoglycaemia, hypokalaemia, hypertension and premature puberty. These distinct phenotypes may suggest that other factors may modify the functional consequences of the R714Q variant of GR.

[Diagnostic and therapeutical significance of macro-TSH in patients with Hashimoto's thyroiditis]. / A makro-TSH diagnosztikus és terápiás jelentosége Hashimoto-thyreoiditises betegekben.

INTRODUCTION: Structure, importance and incidence and clinical role of macro-TSH not clarified in thyroid diseases. AIM: This study was undertaken to determine the incidence and biological role of macro-TSH in patients with Hashimoto's thyroiditis. METHOD: Blood samples taken from patients with Hashimoto's thyroiditis were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with protein G agarose absorption test and gel filtration chromatography. Stimulatory capacity of macro-TSH was measured by CHO cells bio-assay. Patients were treated with L-thyroxine (mean 66.5 µg/day) and half of them with selenium (mean 60 µg/day), respectively. RESULTS: 880 patients (728 female, aged 44.8 yr) with Hashimoto's thyroiditis was involved in the study. Macro-TSH was found in the serum of 41 patients (4.6%), the mean TSH 185.4 ± 35 IU/l was before PEG precipitations and after 5.55 ± 1.8 IU/l. Titre of anti-TPO proved to be 445 ± 51 IU/l and gradulally decreased to 212 ± 51 IU/l after one year therapy. Both the precipitation, protein G absorption and gel chromatography supported the presence of anti-TSH antibody in the macro-TSH complex. Stimulatory capacity of macro-TSH on CHO bio-assay was not proved. The macro-TSH was detected in the selenium not treated group for 18 ± 3.2 months, selenium-treated for 12 ± 1.9 months. CONCLUSION: It is concluded that anti-human TSH autoantibodies are a major components of macro-TSH and may cause diagnostic and therapeutical difficulties. The PEG precipitation is a suitable screening method for detection of macro-TSH. Selenium is able to decrease of anti-TPO antibodies and macro-TSH, respectively. When the TSH level is greater than 40.0 IU/l, without the signs of hypothyroidism, the presence of macro-TSH is to be considered. Orv Hetil. 2017; 158(34): 1346-1350.

Fluorescence activated cell sorting followed by small RNA sequencing reveals stable microRNA expression during cell cycle progression.

BACKGROUND: Previously, drug-based synchronization procedures were used for characterizing the cell cycle dependent transcriptional program. However, these synchronization methods result in growth imbalance and alteration of the cell cycle machinery. DNA content-based fluorescence activated cell sorting (FACS) is able to sort the different cell cycle phases without perturbing the cell cycle. MiRNAs are key transcriptional regulators of the cell cycle, however, their expression dynamics during cell cycle has not been explored. METHODS: Following an optimized FACS, a complex initiative of high throughput platforms (microarray, Taqman Low Density Array, small RNA sequencing) were performed to study gene and miRNA expression profiles of cell cycle sorted human cells originating from different tissues. Validation of high throughput data was performed using quantitative real time PCR. Protein expression was detected by Western blot. Complex statistics and pathway analysis were also applied. RESULTS: Beyond confirming the previously described cell cycle transcriptional program, cell cycle dependently expressed genes showed a higher expression independently from the cell cycle phase and a lower amplitude of dynamic changes in cancer cells as compared to untransformed fibroblasts. Contrary to mRNA changes, miRNA expression was stable throughout the cell cycle. CONCLUSIONS: Cell cycle sorting is a synchronization-free method for the proper analysis of cell cycle dynamics. Altered dynamic expression of universal cell cycle genes in cancer cells reflects the transformed cell cycle machinery. Stable miRNA expression during cell cycle progression may suggest that dynamical miRNA-dependent regulation may be of less importance in short term regulations during the cell cycle.

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

OBJECTIVE: Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. CONTEXT: To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. PATIENTS AND METHODS: 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. RESULTS: The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. CONCLUSION: The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients.

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy.

Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

Cord serum dipeptidyl-peptidase 4 activity in gestational diabetes.

BACKGROUND: Tissue-specific dipeptidyl-peptidase 4 (DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 -incretin system has not been studied in foetal life. In this study, DPP4 activity and glucagon-like peptide-1 (GLP-1) levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus (GDM) and nondiabetic controls. MATERIAL AND METHODS: This study has been conducted in two Hungarian and one Austrian centres. PATIENTS: A total of 568 pregnant women were enrolled in the study after their OGTT between the 24th and 28th gestational week. Cord blood samplings with DPP4 activity and GLP-1 level measurements were possible in 270 (DPP4: 159 control, 111 GDM) and 112 (GLP-1: 72 control, 40 GDM) cases. OGTT (24-28th gestational week) and cord blood sampling at delivery were performed. Cord serum DPP4 activity was determined in a continuous monitoring microplate-based kinetic assay, and cord plasma GLP-1 was measured using a fluorescence ELISA method. RESULTS: Cord serum DPP4 activity was lower in GDM [mean (95% CI): 28.07 U/L (26.32-29.82 U/L)] than in controls [31.61 U/L (29.93-33.29 U/L), MWU P = 0.0015]. Cord plasma active GLP-1 levels were close to the lower detection limit and were not altered in GDM (control: mean = 3.43 pM, 95% CI: 3.04-3.82 pM, GDM: mean = 3.61 pM, 95% CI: 2.96-4.28 pM - MWU test P = 0.6). CONCLUSIONS: Decreased cord serum DPP4 activity in gestational diabetes mellitus might be the result of an adaptive foetal response or an early dysregulation in the entero-insular axis with consequences beyond the incretin system. Cord plasma GLP-1 levels may reflect the missing oral intake with a limited glucose sensing of L cells via the circulation in foetal life.

Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer.

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.

Antioxidant effect of the active metabolites of tibolone.

Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M) of either estradiol, tibolone, 3α-hydroxytibolone, 3ß-hydroxytibolone, Δ(4)-tibolone, 3α-sulfated-tibolone, 3α-17ß-disulfated-tibolone, 3ß-sulfated-tibolone or 3ß-17ß-disulfated-tibolone. Superoxide anion generation of neutrophils was measured by photometry. Results of different steroids were given as percentages of their controls. A more simple superoxide generating system, the xanthine-xanthine oxidase reaction was also tested. We found that granulocyte superoxide production did not differ from the control using 10(-9 )M of steroids. Using 10(-8 )M concentration: estradiol (80.9 ± 2.5%); 3ß-sulfated-tibolone (83.3 ± 4.7%); 3ß-17ß-disulfated-tibolone (81.0 ± 4.2%) caused a significant decrease in superoxide production, compared to the control. In addition at 10(-7 )M, 3ß-hydroxytibolone and 3α-sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine oxidase system estradiol (67.4 ± 1.0%), 3α-sulfated-tibolone (85.8 ± 5.3%), 3α-17ß-disulfated-tibolone (71.9 ± 2.5%), 3ß-sulfated-tibolone (73.9 ± 5.0%), and 3ß-17ß-disulfated-tibolone (65.8 ± 3.4%) caused a significant decrease in superoxide production. Conclusively, although tibolone itself did not show significant antioxidant capacity, most of its active metabolites have antioxidant effects.

[Novel methods and their applicability in the evaluation of the genetic background of endocrine system tumours]. / Új módszertani lehetoségek és ezek alkalmazása a hormonális rendszer daganatainak genetikai kivizsgálásában.

The technical developments leading to revolution in clinical genetic testing offer new approaches for patients with cancer. From one mutation or one gene approach the scale of genetic testing moved to whole exome or whole genome scale. It is well known that many tumours are genetically determined and they are part of familial tumour syndromes. In addition, some mutations indicate specific molecular targeted therapies. Although sampling and sample preparation are different for testing germline and somatic mutations, the technical background of the analysis is the same. The aim of clinical genetic testing is to identify patients who are carriers of disease-causing mutations or to test tumour tissue for the presence of genetic alterations which may be targets for therapeutic approaches. In this review the authors summarize novel possibilities offered by next-generation sequencing in clinical genetic testing of patients with endocrine tumours. In addition, the authors review recent guidelines on technical and ethical issues related to these novel methods.

[Analysis of laboratory data of 155 patients with pheochromocytoma-paraganglioma syndrome diagnosed during the past 20 years]. / A laboratóriumi diagnosztika eredményei az elmúlt 20 évben kórismézett 155 phaeochromocytoma/paraganglioma szindrómás beteg adatainak elemzése alapján.

INTRODUCTION: Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades. AIM: Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University. METHOD: Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry. RESULTS: Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively). CONCLUSIONS: These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

Analysis of circulating microRNAs in adrenocortical tumors.

Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumors (ACTs) is entirely different. Circulating microRNAs (miRNAs) are promising biomarker candidates of malignancy in several tumors; however, there are still numerous technical problems associated with their analysis. The objective of our study was to investigate circulating miRNAs in ACTs and to evaluate their potential applicability as biomarkers of malignancy. We have also addressed technical questions including the choice of profiling and reference gene used. A total of 25 preoperative plasma samples obtained from patients with ACAs and carcinomas were studied by microarray and quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197 and hsa-miR-1281) found as differentially expressed in plasma samples in our microarray screening could be validated by quantitative real-time PCR. In contrast, of the selected eight miRNAs reported in the literature as differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR-184, hsa-miR-210 and hsa-miR-483-5p) showed a statistically significant overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16 as a reference gene. Receiver operator characteristic analysis of data revealed that the combination of dCThsa-miR-210 - dCThsa-miR-181b and dCThsa-miR-100/dCThsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87 and 0.85, respectively). In conclusion, we have found significant differences in expression of circulating miRNAs between ACAs and carcinomas, but their diagnostic accuracy is not yet high enough for clinical application. Further studies on larger cohorts of patients are needed to assess the diagnostic and prognostic potential application of circulating miRNA markers.

Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome.

The HSD11B1 gene encodes the type 1 isoform of the 11-ß-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells.

The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study.

BACKGROUND: The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity. METHODS: Human polymorphonuclear leukocytes (PMN) were incubated with opsonised Escherichia coli and either MPO, indomethacin, estradiol, or hydrocortisone. Intracellular killing capacity was evaluated with UV microscopy after treatment with fluorescent dye. Next, an in vivo experiment was performed with nine groups of rats: in the first phase of the study indomethacin treatment and Pasteurella multocida infection (Ii), indomethacin treatment without infection (I0), untreated control with infection (Mi) and untreated control without infection (M0); in the second phase of the study rats with infection and testosterone treatment (NT), castration, infection and testosterone treatment (CT), castration, infection and estradiol treatment (CE), non-castrated infected control (N0), and castrated infected control (C0). After treatment bacteria were reisolated from the liver and heart blood on agar plates, and laboratory parameters were analyzed. For the comparison of laboratory results ANOVA or Kruskal-Wallis test and LSD post hoc test was used. RESULTS: Indomethacin did not have a remarkable effect on the bacterial killing of PMNs, while the other compounds increased bacterial killing to various degrees. In the animal model indomethacin and infection caused a poor clinical state, a great number of reisolated bacteria, elevated white blood cell (WBC) count, decreased C-reactive protein (CRP) and serum albumin levels. Testosterone treatment resulted in less bacterial colony numbers in group NT, but not in group CT compared to respective controls (N0, C0). Estradiol treatment (CE) decreased colony numbers compared to control (C0). Hormone administration resulted in lower WBC counts, and in group CE, a decreased CRP. CONCLUSIONS: MPO, estradiol, and hydrocortisone improve bacterial killing activity of PMNs. Indomethacin treatment and castration weaken immune responses and clinical state of infected rats, while testosterone and estradiol have a beneficial effect.

[Significance of biochemical markers in the diagnosis of neuroendocrine tumours and for the follow-up of patients]. / Biokémiai markerek jelentosége a neuroendokrin daganatok felismerésében és a betegek követésében.

Circulating markers of neuroendocrine tumours are useful tools in the diagnosis of these tumours. Laboratory tests for general biomarkers have acceptable sensitivity for the recognition of neuroendocrine tumours as these biologically active proteins are typically synthesized by all types of neuroendocrine cells. Measurement of chromogranin A is widely used not only in the diagnosis of neuroendocrine tumours but it may predict the prognosis of the diseases and the effect of the antitumor therapy. It is also a useful tool for the detection of residual tumours. Neurendocrine tumours represent a heterogeneous group of tumours with the ability to secrete several hormones and, therefore, measurement of these hormones can also serve as neuroendocrine cell type-specific markers in routine clinical practice. In this review the authors summarize the significance of tumour markers in the diagnosis of neuroendocrine tumours as well as in the management and follow-up of patients with this disease.

[Effects and significance of estradiol in men]. / Az ösztradiol hatásai és jelentosége férfiakban.

The most important estrogen is estradiol in both men and women. In men elevated estradiol levels and associated metabolic disorders have been implicated in the development of common diseases including cardiovascular disorders, insulin resistance and type 2 diabetes mellitus, as increased estradiol associated with decreased testosterone levels increases the risk of these diseases. In this review the authors summarize the causes and consequences of androgen deficiency and estradiol excess, and they review recent studies on potential therapeutic strategies to correct increased estradiol levels in men.

[Neurovascular compression of the medulla oblongata: a rare cause of secondary hypertension]. / Nyúltveloi neurovascularis kompresszió. A szekunder hypertonia ritka oka.

Compression of the rostral ventrolateral medulla oblongata is one of the rarely identified causes of refractory hypertension. In patients with severe, intractable hypertension caused by neurovascular compression, neurosurgical decompression should be considered. The authors present the history of a 20-year-old man with severe hypertension. After excluding other possible causes of secondary hypertension, the underlying cause of his high blood pressure was identified by the demonstration of neurovascular compression shown by magnetic resonance angiography and an increased sympathetic activity (sinus tachycardia) during the high blood pressure episodes. Due to frequent episodes of hypertensive crises, surgical decompression was recommended, which was performed with the placement of an isograft between the brainstem and the left vertebral artery. In the first six months after the operation, the patient's blood pressure could be kept in the normal range with significantly reduced doses of antihypertensive medication. Repeat magnetic resonance angiography confirmed the cessation of brainstem compression. After six months, increased blood pressure returned periodically, but to a smaller extent and less frequently. Based on the result of magnetic resonance angiography performed 22 months after surgery, re-operation was considered. According to previous literature data long-term success can only be achieved in one third of patients after surgical decompression. In the majority of patients surgery results in a significant decrease of blood pressure, an increased efficiency of antihypertensive therapy as well as a decrease in the frequency of highly increased blood pressure episodes. Thus, a significant improvement of the patient's quality of life can be achieved. The case of this patient is an example of the latter scenario.

[The role of selenium in endocrine system diseases]. / A szelén szerepe az endokrin betegségekben.

Oxygen derived free radicals, generated by a number of cellular reactions, include superoxide anion, hydrogen peroxide and hydroxyl radicals. They exert their cytotoxic effects mainly via peroxidation of the cell membrane resulting in the loss of membrane integrity. The essential trace element, selenium exerts complex effects on the endocrine systems, partly due to its antioxidant capacity. Well-characterized selenoproteins include iodothyronine deiodinases, glutathione peroxidases and thioredoxin reductases involved in thyroid hormone metabolism and protection from oxidative damage. The value of selenium supplementation in autoimmune thyroid disorders has been investigated and most studies confirmed the beneficial effect of selenium supplementation in Hashimoto's and Graves's diseases. Recently, selenium proved to be effective in mild inflammatory orbitopathy. There are a number of reports about the effect of selenium in diabetes mellitus, but the data are controversial as both insulin-like and diabetes-inducing effects of selenium have been described. Selenium was successfully used in both female and male infertility of autoimmune origin.

[The "blue man"]. / A "kék ember"

The authors present the case of a 63-year-old man who was evaluated for symptoms of lung fibrosis, blue face and epithelopathy affecting both eyes. All these symptoms could be attributed to the adverse effects of amiodarone. Thyroid disorders, which are the most common side-effects of amiodarone treatment were absent. The authors want to draw attention to the potential side effects of amiodarone.

[Carcinoid heart disease]. / Carcinoid szívbetegség.

Carcinoids are rare tumors originating from neuroendocrine cells. A large proportion of these tumors produce serotonin and other biologically active hormones which may produce carcinoid syndrome characterized by flushing, diarrhoea and bronchospasm. Carcinoid heart disease, a rare complication of carcinoid syndrome, may itself have a great impact on life expectancy of patients with carcinoid syndrome. The authors present a case history of a patients with carcinoid heart disease and they review the symptoms, diagnosis and therapeutic options of this rare complication of carcinoid syndrome.

[A rare form of adrenal Cushing's syndrome]. / Ritka etiológiájú Cushing-szindróma.

The authors present the case history of a 74-year-old male suffering from aortic coarctation. His endocrine evaluation was initiated because of severe hypokalemia. The diagnostic procedures revealed the presence of Cushing's syndrome caused by bilateral macronodular adrenal hyperplasia. Because of the high risk of surgical treatment due to his cardiac condition, the patient was treated with the steroid biosynthesis inhibitor ketoconazole, which resulted in a clinical and biochemical regression of hypercortisolism. After interventional treatment of the aortic coarctation the physical and cardiac condition of the patient showed a significant improvement, indicating that despite an old age, surgery offered a valuable tool for management of the disease. To the best knowledge of the authors, the coexistence of aortic coarctation and bilateral macronodular adrenal hyperplasia has not been previously reported. Orv. Hetil., 154(50), 1999-2002.